Clinical and imaging findings,treatments, and outcomes in 27 dogs with imaging diagnosed trigeminal nerve sheath tumors: A multi‐center study

The clinical behavior of canine trigeminal nerve sheath tumors and benefits of previously reported treatments are incompletely defined. Aims of this retrospective, multicenter, observational study were to describe clinical signs, tumor localization characteristics, treatments, and clinical outcomes in a group of dogs with this neoplasm. Databases at four hospitals were reviewed for dogs with a trigeminal nerve sheath tumor diagnosis, magnetic resonance imaging (MRI) studies, and presentation between 2004 and 2014. A single observer recorded medical record findings and two observers recorded MRI characteristics by consensus. A total of 27 dogs met inclusion criteria (15 treated with stereotactic radiation therapy and 12 unirradiated). Two unirradiated dogs were excluded from outcome analyses. The most common presenting signs were masticatory muscle atrophy (26 dogs), neurologic signs referable to intracranial disease (13), and ocular disease (12). Based on MRI findings, all dogs had disease extending centrally at the level of the brainstem. The most commonly affected trigeminal nerve branches were the mandibular (26 dogs), maxillary (22), and ophthalmic (10). Of 15 dogs treated with stereotactic radiation therapy, one had improved muscle atrophy, and six had poor ocular health after treatment. Neurologic signs improved in 4/5 dogs with intracranial signs. Overall median survival time for the 10 unirradiated dogs with available follow‐up was 12 days and 441 days for the 15 stereotactic radiation therapy dogs. Mean survival times between these groups were not significantly different (mean 95% CI for unirradiated dogs was 44–424 days and mean 95% CI for stereotactic radiation therapy dogs was 260–518 days).     

Surgical decompression,with or without adjunctive therapy,for palliative treatment of primary vertebral osteosarcoma in dogs

Vertebral osteosarcoma (OSA) is the most common primary vertebral tumor in dogs, however studies examining the survival time after surgical decompression of these tumors are limited. There is also limited information regarding the benefit of adjunctive treatments such as radiation therapy or chemotherapy in these patients. The goal of this study was to determine survival time of dogs with primary vertebral OSA after palliative decompressive surgery alone and combined with radiation therapy and/or chemotherapy. Records from 22 client‐owned dogs diagnosed with primary vertebral OSA and treated with decompressive surgery were collected retrospectively from eight referral institutions. Survival time was assessed for dogs treated with surgery alone as well as dogs who received adjunctive radiation therapy and/or chemotherapy. Median survival time in the 12 dogs treated with surgery alone was 42 days (range: 3‐1333 days). The three dogs treated with surgery and chemotherapy had a median survival time of 82 days (range: 56‐305 days). Only one dog was treated with surgery and radiation therapy; this dog survived 101 days. Six dogs were treated with surgery, radiation therapy and chemotherapy; these dogs had a median survival time of 261 days (range: 223‐653 days). Cause of death in all cases that survived the initial postoperative period was euthanasia secondary to confirmed or suspected tumor regrowth. The results of this study suggest that definitive radiation therapy, possibly combined with concurrent chemotherapy, significantly improves survival in dogs treated with palliative decompressive surgery for vertebral OSA and should be the treatment of choice in selected cases.     

Half-Body Radiotherapy in the Treatment of Canine Lymphoma

In a Phase I-II study, half-body radiotherapy was used to treat 14 dogs with multicentric lymphoma. Using this technique, a radiation dose of 7 Gray (Gy) was delivered to one half of the body in a single exposure. The other half of the body was treated approximately 28 days later. Of 14 treated dogs, 11 (79%) had a measurable decrease in tumor size. Five dogs achieved a complete or partial remission with a mean duration of 102 and 54 days, respectively. In predicting response to therapy, poor prognostic factors included large tumor burdens, advanced disease stage, and chemotherapy-resistant tumors. Side effects of treatment were divided chronologically into acute (radiation sickness, tumor lysis), subacute (bone marrow suppression), and chronic (radiation pneumonitis, lymphoma-cell leukemia) syndromes. Complications were more severe in tumor-bearing dogs when compared with healthy control animals. Dogs with small tumor burdens and minimal internal disease had fewer complications compared with those with more advanced disease.     

Surgery alone or in combination with radiation therapy for treatment of intracranial meningiomas in dogs: 31 cases (1989-2002)

OBJECTIVE: To compare, for dogs with intracranial meningiomas, survival times for dogs treated with surgical resection followed by radiation therapy with survival times for dogs treated with surgery alone. DESIGN: Retrospective study. ANIMALS: 31 dogs with intracranial meningiomas. PROCEDURE: Medical records of dogs with histologic confirmation of an intracranial meningioma were reviewed. For each dog, signalment, clinical signs, tumor location, treatment protocol, and survival time were obtained from the medical record and through follow-up telephone interviews. RESULTS: Dogs that underwent tumor resection alone and survived > 1 week after surgery had a median survival time of 7 months (range, 0.5 to 22 months). Dogs that underwent tumor resection followed by radiation therapy had a median survival time of 16.5 months (range, 3 to 58 months). CONCLUSIONS AND CLINICAL RELEVANCE: Results suggest that in dogs with intracranial meningiomas, use of radiation therapy as a supplement to tumor resection can significantly extend life expectancy.     

Evaluation of survival time in dogs with stage III osteosarcoma that undergo treatment: 90 cases (1985-2004)

OBJECTIVE-To assess survival time in dogs that underwent treatment for stage III osteosarcoma and evaluate factors affecting survival. DESIGN-Retrospective case series. ANIMALS-90 dogs with stage III osteosarcoma. PROCEDURES-Records in the osteosarcoma database at the Animal Cancer Center at Colorado State University from 1985 to 2004 were searched for dogs with metastatic disease at the time of evaluation. Dogs were included in the study if they had metastasis to any site and if treatment was initiated. A Kaplan-Meier survival analysis was performed, and the influences of age, sex, breed, primary tumor site, metastatic sites, and treatment on outcome were analyzed via log-rank analysis. RESULTS-Median survival time was 76 days, with a range of 0 to 1,583 days. No significant differences in survival times on the basis of age, sex, breed, or primary site were observed. Breeds and primary tumor sites were typical of those usually associated with osteosarcoma in dogs. Dogs treated palliatively with radiation therapy and chemotherapy had a significantly longer survival time (130 days) than dogs in all other treatment groups. Dogs treated with surgery alone had a significantly shorter survival time (3 days) than dogs treated with surgery and chemotherapy (78 days). Dogs with bone metastases had a longer survival time than dogs with soft tissue metastases. CONCLUSIONS AND CLINICAL RELEVANCE-Treatment of dogs with stage III osteosarcoma can result in various survival times. Dogs with metastasis to bone and dogs that were treated palliatively with radiation and chemotherapy had the longest survival times.     

Effects of radiotherapy alone and surgery and radiotherapy on survival of dogs with nasal tumours

The case records of 26 dogs with nasal tumours, treated either with radiation alone or surgery and radiation, were compared. One- and two-year actuarial survival rates for 12 dogs treated with radiotherapy were 58 and 13 per cent, respectively, compared to 71 and 38 per cent, respectively, for 14 dogs which were treated with surgery before radiotherapy. Sixty-seven per cent of the dogs treated with radiotherapy had recurrent clinical signs by 52 weeks compared to 36 per cent of the dogs treated with surgery and radiotherapy. The longer disease-free interval of the dogs treated with surgery and radiotherapy was statistically significant. When dogs with sarcomas were compared to those with carcinomas, there was no significant difference in disease-free interval or survival time.     

Intraoperative Irradiation of 16 Spontaneously Occurring Canine Neoplasms

Sixteen dogs with malignant neoplasms were treated with intraoperative radiation therapy after surgical debulking. Fractionated external beam radiation therapy was given postoperatively to 11 dogs. Healing of surgical incisions was uncomplicated in 14 dogs. When the ureters or urinary bladder were included in the irradiation field, they became stenotic and fibrotic. Urinary incontinence and secondary renal injury were common. Local tumor control was poor regardless of site or tumor type.     

FACTORS INFLUENCING SURVIVAL AFTER RADIOTHERAPY OF NASAL TUMORS IN 130 DOGS

Improvements in survival of dogs with nasal tumors have been slow to develop throughout the past three decades. Despite multiple studies examining various radiation time-dose schema, the advancement of CT-based computerized treatment planning, and the evaluation of detailed staging systems, the optimal treatment regimen, and most important prognostic factors regarding survival remain unclear. In this study, data from four previous studies were combined with data from 44 additional dogs, and this population of 130 dogs was evaluated for factors which influenced survival. Twenty-one dogs were treated with orthovoltage at the University of Pennsylvania. One hundred nine dogs were treated with cobalt photons at North Carolina State University. Sixty-five of these 109 dogs had been previously described. Of the 44 dogs not previously described, 35 were treated with a shrinking field technique. Survival was determined from the medical record, or from information derived by telephone or mail survey. The univariate Cox regression model was used to examine for relationship between various patient, tumor, and treatment variables and survival. Significant relationships identified in the univariate analysis were further analyzed using the multivariate Cox regression model. Median survival of the 130 dogs was 8.9 months (95% C.I., 8-11 months). In the univariate analysis, the following variables were associated with decreased survival: 1) age >10 years old, 2) regional lymph node metastasis, 3) advanced tumor stage, 4) use of megavoltage radiation, 5) overall total dose >55 Gray, and 6) boost technique performed. In a multivariate analysis of 125 dogs with complete data for age, radiation type, and radiation dose, age (p < .001) and radiation type (p = .02) were identified as joint predictors of survival. After adjusting for age, the staging system lost prognostic significance (p = .06). In a subset of dogs that received cobalt radiation, after adjusting for age, dogs treated with a boost technique had decreased survival (p = .001). In general, local control of canine nasal tumors following aggressive radiation therapy is poor. Early diagnosis and selection of appropriate patients is warranted and palliative types of treatment should be considered in dogs with a poor chance of long term survival.     

Retrospective analysis of nonradiation complications in dogs undergoing radiation therapy

Dogs receiving radiation can develop complications unrelated to the radiation treatment. No study to date has described these complications in clinical patients undergoing multiple radiation therapy treatments. The purpose of this retrospective case‐control study was to characterize the incidence and type of complications that occur in these dogs. A secondary goal was to evaluate whether patient and treatment characteristics could be identified to predict the risk of these complications. Medical records of 268 dogs receiving at least one radiation treatment at a single institution, between September, 2004 and June, 2007 were reviewed. Age, breed, gender, body weight, tumor type, tumor location, number of treatments, pre‐treatment blood work abnormalities, and whether chemotherapy, glucocorticoids, or nonsteroidal anti‐inflammatory drugs were given were collected. Number, type, and severity of nonradiation complications were recorded. Complications attributed to the tumor or to the radiation were excluded. Statistical analyses were performed to determine whether demographic and clinical characteristics were associated with development of a complication. General anesthesia was used for all treatments. Complications occurred in 101 (37%) cases including diarrhea, vomiting, cough, and loss of appetite, which were typically mild. Seventeen dogs (6%) developed severe complications. Eight dogs (3%) died from their complication. Dogs that developed complications were younger, received more treatments, had leukocytosis, received glucocorticoids, and were less likely to have thrombocytopenia. On multivariate analysis, number of treatments and leukocytosis were significantly associated with complications. Findings indicate that nonradiation complications are common in dogs receiving radiotherapy under general anesthesia. In this population, complications were usually mild or self‐limiting.     

Alpha-fetoprotein in serum and tumor tissues in dogs with hepatocellular carcinoma.

Serum alpha-fetoprotein (AFP) concentrations were measured before and after surgical removal of tumor masses in four dogs with hepatocellular carcinoma (HCC). Localization of AFP was also examined immunohistochemically in tumor tissues. In three cases, the serum AFP concentration was 10 to 20 times higher than that of normal dogs. One to two months after surgery, the serum AFP concentration had decreased to normal range. AFP was localized in the tumor tissues in these three cases. One case, which had a low serum AFP, did not show AFP localization in tumor tissue.     

AN ACCELERATED TECHNIQUE FOR IRRADIATION OF MALIGNANT CANINE NASAL AND PARANASAL SINUS TUMORS

Tumor and normal tissue response was assessed in 21 dogs with malignant nasal tumors given 42 Gy cobalt radiation in 9 or 10 fractions over 11 to 13 days. Local tumor/clinical relapse recurred in 68% of dogs, with a median relapse free interval (RFI) of 270 days. Median survival was 428 days. One year survival for all dogs was 60%. RFI and survival times are better than, or similar to, previous reports of dogs treated with radiotherapy only. Acute radiation effects were severe in one dog. Late effects were severe in six of 15 dogs (40%) with durable tumor control. Late effects included bilateral blindness (3), osteoradionecrosis (3), and seizures (1). These six dogs had a median survival of 705 days. Loss of vision occurred in at least one eye in nine dogs (47%). Tumor staging based on CT findings were predictive for survival duration. Tumor histology was not predictive of outcome. Labrador Retrievers were significantly over-represented. Despite comparable or improved tumor control and survival times provided by this accelerated protocol, relative to other radiotherapy reports, local failure remains the major cause of death, and late radiation effects can be severe in dogs with durable tumor control.     

Radiotherapy of brain tumors in dogs

Brain tumors in 4 dogs were treated with external beam, megavoltage radiation. X-ray computed tomography was used to localize and characterize brain tumors and to assess treatment response. Total radiation doses were 3,000 or 3,600 rad, given in 5 or 6 fractions over 14 to 19 days. Complete tumor regression, as determined from computed tomography scans, improvement in clinical signs, and reduction in medication, were documented in all irradiated dogs. The median survival time for irradiated dogs was 322 days, which was significantly (P less than 0.05) longer than the median survival time of 56 days in 8 dogs with brain tumors treated symptomatically. The one-year survival rate for the irradiated dogs, after correcting for deaths from intercurrent disease, was 100%. It was concluded that canine brain tumors may be treated effectively by use of megavoltage radiation.     

Clinical outcome in dogs with nasal tumors treated with intensity-modulated radiation therapy

Intensity-modulated radiation therapy (IMRT) is a valuable tool in human radiation oncology, but information on its use in veterinary medicine is lacking. In this study, 12 dogs with nasal tumors were treated with IMRT at a median radiation dose of 54 Gy. Patient survival times and frequency and severity of side effects on ocular structures, oral mucosa, and skin were recorded. Eight dogs (67%) had resolution of clinical signs during radiation therapy. Median overall survival time was 446 d with a 50% 1-year and a 25% 2-year survival rate. Minimal grade 2 or 3 acute skin toxicity, no grade 2 or 3 late skin toxicity, and no grade 2 or 3 toxicity to oral mucosa or the eye opposite the tumor were identified in the dogs treated with IMRT in this study. The ipsilateral eye could not be routinely spared due to its proximity to the tumor.     

Hypothyroidism in the dog: a retrospective study of sixteen cases

Sixteen dogs with confirmed hypothyroidism were reviewed. The diagnosis was based on subnormal plasma thyroxine concentration and poor response following TSH administration. Common clinical signs were alopecia (12 dogs), lethargy (11) and obesity (11). Plasma cholesterol concentrations were abnormally high in 10 of 14 cases tested, five of 12 were anaemic and three of five had increased creatine phosphokinase activity. Skin changes compatible with endocrinopathy were present in all five cases biopsied. Spontaneous muscle activity was found on electromyography in four cases so examined. All dogs were treated with sodium levothyroxine, and 10 of 13 for which information was available responded satisfactorily.     

Intraoperative radiotherapy of carcinoma of the prostate gland in ten dogs

Ten dogs with carcinoma of the prostate gland were treated with intraoperative orthovoltage radiotherapy (radiation therapy to surgically exposed tumors). Seven dogs had tumor growth confined to the prostate gland and urethra, and 3 dogs had carcinoma of the prostate gland and regional lymph node involvement. Total radiation doses delivered to the prostate gland of 9 dogs and the affected regional lymph nodes of 3 dogs, using orthovoltage x-rays, ranged from 20 to 30 Gy. Carcinoma of the prostate gland of one dog was intraoperatively irradiated to 15 Gy and was then given a boost of 40 Gy, using cobalt-60 teletherapy. Survival time ranged from 41 to 750 days after intraoperative radiotherapy. Median and mean survival times for all dogs were 114 and 196 days, respectively. The median survival time for 7 dogs with localized prostatic carcinoma was 180 days, which was longer, but not significantly longer (P = 0.09), than the median survival time of 80 days in 3 dogs having prostatic carcinoma and metastatic disease. Intraoperative radiotherapy was tolerated well and caused complete response in 5 dogs. However, surgical complications in 2 dogs, which had subtotal lymphadenectomy or prostatic biopsy performed concurrently at the time of irradiation, resulted ultimately in their deaths. The 2 other dogs with metastatic disease and 1 dog without metastatic disease also had poor response to treatment. Our results indicated that intraoperative radiotherapy is an effective treatment for localized prostatic carcinoma in the dog.     

DEFINITIVE RADIATION THERAPY FOR INFILTRATIVE THYROID CARCINOMA IN DOGS

The medical records of eight dogs with histopathologically confirmed infiltrative thyroid carcinoma treated with external beam radiation were reviewed and a retrospective analysis of survival and local tumor control were performed. The dogs received a definitive radiotherapy protocol of 46.8-48 Gray. All dogs had a reduction in tumor size to a clinically undetectable level on follow up examinations. Kaplan-Meier analysis indicated a median survival time of 24.5 months. Pulmonary metastasis was detected in three dogs and one of these dogs had concurrent bone metastasis. One dog had bone metastasis alone. Two dogs were alive at the censor. This study suggests that fractionated, definitive radiation therapy using multiple, moderate doses of radiation is an effective treatment for local control of invasive thyroid carcinoma in dogs.     

Prolonged survival after craniectomy with skull reconstruction and adjuvant definitive radiation therapy in three dogs with multilobular osteochondrosarcoma

Multilobular osteochondrosarcoma is an uncommon canine tumor but presents a treatment challenge when arising on the skull. This retrospective case series study aimed to describe outcome of a multimodality treatment approach involving aggressive surgical resection and adjuvant definitive radiation therapy in a group of dogs with multilobular osteochondrosarcoma of the calvarium. Clinical, imaging, treatment, and outcome data were collected from retrospective review of medical records. Three dogs met inclusion criteria. The presenting clinical complaint was the presence of a mass effect of the skull in all three dogs and concurrent neurologic abnormalities in one dog. Advanced imaging revealed aggressive lytic and proliferative tumors arising from the calvarium in all three dogs. All dogs were treated surgically with a modified craniectomy, repaired with a titanium mesh—polymethyl methacrylate bone cement implant or a low prolife titanium mesh plate and followed by adjuvant definitive radiation therapy with 2.5 Gy per fraction for 22 daily fractions. There were no major immediate surgical complications and radiation was well tolerated overall. Neurologic improvement was seen in the patient that presented with neurologic disease. Survival times from surgery were 387, 422, and 730 days and from the time of radiation were 358, 397, and 677 days. Findings in this sample of three dogs supported the use of aggressive therapy with a combination of surgical craniectomy and cranioplasty utilizing a titanium mesh implant and high dose definitive radiation therapy for local control and prolonged survival times in dogs with multilobular osteochondrosarcoma of the skull.     

Retroperitoneal sarcomas in dogs: 14 cases (1992-2002)

OBJECTIVE: To describe the clinical features, surgical and histologic findings, biological behavior, and outcome of dogs with retroperitoneal sarcomas. DESIGN: Retrospective study. ANIMALS: 14 dogs. PROCEDURES: Medical and pathology records from 1992 to 2002 of dogs with tumors originating in the retroperitoneal space were reviewed. Dogs with retroperitoneal tumors originating from the adrenal glands, kidneys, or ureters were excluded. Inclusion criteria included observation of a tumor arising from the retroperitoneal space during exploratory surgery or necropsy and histologic confirmation of tumor type. Details of clinical signs, diagnostic findings, surgical management, and outcome were determined from medical records and telephone interviews with veterinarians and owners. RESULTS: Retroperitoneal sarcoma was diagnosed in 14 dogs, 2 at necropsy and 12 during exploratory surgery. Hemangiosarcoma was the most common histologic diagnosis. Seven dogs had regional extension of the sarcoma into adjacent organs, and 4 dogs had metastatic disease. Grossly complete resection was possible in 6 dogs. Cytoreductive surgery or incisional biopsy was performed in the remaining dogs. Two dogs were treated with palliative radiation therapy (1 intraoperatively and 1 postoperatively). Three dogs received adjunctive chemotherapy, although none completed the targeted course because of development of local recurrence or metastatic disease. Local recurrence was reported in 2 of 12 dogs and metastasis in 10 of 14 dogs. Thirteen dogs died or were euthanatized as a result of the retroperitoneal sarcoma; 1 dog was alive and disease-free 410 days after surgery. Median survival time was 37.5 days. CONCLUSIONS AND CLINICAL RELEVANCE: In dogs, retroperitoneal sarcomas are aggressive tumors with a high rate of local recurrence and metastasis, and a poor survival time.     

Clinical assessment of a chemosensitivity assay as a treatment planning tool for dogs with cancer

This study evaluated the clinical utility of a commercially available chemosensitivity assay. In the first part of the study, tumor tissues from dogs with various malignancies were tested, and the dogs were treated with a mitoxantrone/cyclophosphamide combination protocol. Tumor response was evaluated and compared to the predicted response. Assay results were not a significant predictor of clinical response to chemotherapy or of survival time. In the second part of the study, assay results were used to direct therapy in dogs with refractory lymphoma. There was no significant correlation (p equals 0.323) between predicted response and case outcome.